525 results on '"Lee, Randall J."'
Search Results
2. A Feasibility Study of [18F]F-AraG Positron Emission Tomography (PET) for Cardiac Imaging–Myocardial Viability in Ischemia–Reperfusion Injury Model
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Shrestha, Uttam M., Chae, Hee-Don, Fang, Qizhi, Lee, Randall J., Packiasamy, Juliet, Huynh, Lyna, Blecha, Joseph, Huynh, Tony L., VanBrocklin, Henry F., Levi, Jelena, and Seo, Youngho
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- 2024
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3. Hybrid epicardial and endocardial sinus node–sparing ablation therapy for inappropriate sinus tachycardia: Rationale and design of the multicenter HEAL-IST IDE trial
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de Asmundis, Carlo, Pannone, Luigi, Lakkireddy, Dhanunjaya, Beaver, Thomas M, Brodt, Chad R, Lee, Randall J, Frazier, Kenneth, Chierchia, Gian-Battista, and La Meir, Mark
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Patient Safety ,Clinical Trials and Supportive Activities ,Cardiovascular ,Inappropriate sinus node tachycardia ,Electrophysio-logical mechanism ,Sinoatrial node ,Catheter ablation ,Hybrid sino-atrial node sparing ablation ,Electrophysiological mechanism ,Hybrid sinoatrial node sparing ablation - Abstract
BackgroundInappropriate sinus tachycardia (IST) is defined as resting heart rate >100 beats/min and average 24-hour heart rate >90 beats/min. It is associated with distressing symptoms and significant loss of quality of life. Drugs are not effective in symptom control of IST in up to 30% of patients. Catheter ablation of the sinus node has a high recurrence rate, and the complications are significant. Recently, a novel hybrid sinus node-sparing ablation approach for IST was described.ObjectiveThe objective of the Hybrid Epicardial and Endocardial Sinus Node Sparing Ablation Therapy for Inappropriate Sinus Tachycardia (HEAL-IST) investigational device exemption trial (NCT05280093) is to evaluate safety and effectiveness of the hybrid sinus node-sparing ablation procedure for the treatment of symptomatic, drug-refractory or drug-intolerant IST.MethodsThe HEAL-IST trial is a prospective, multicenter, pivotal, single-arm trial. Up to 142 subjects in up to 40 centers will be treated in the trial with a Bayesian adaptive design.ResultsSubjects will be assessed for primary safety through 30 days post-hybrid ablation procedure. The primary effectiveness endpoint will be freedom from IST at 12 months. Freedom from IST will be defined as mean heart rate of ≤90 beats/min or at least a 15% reduction in mean heart rate as compared with baseline, in the absence of new or higher dosage of previously failed medications at a 24-month follow-up assessment.ConclusionThe HEAL-IST trial is the first multicenter trial evaluating hybrid IST ablation in patients with symptomatic IST and refractory or intolerant to drugs. The results of this study will help guide decision making regarding the best management in this population.
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- 2023
4. Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after myocardial infarction
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Mohindra, Priya, Zhong, Justin X, Fang, Qizhi, Cuylear, Darnell L, Huynh, Cindy, Qiu, Huiliang, Gao, Dongwei, Kharbikar, Bhushan N, Huang, Xiao, Springer, Matthew L, Lee, Randall J, and Desai, Tejal A
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Medical Biotechnology ,Medical Physiology ,Biomedical and Clinical Sciences ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Medical biotechnology ,Medical physiology - Abstract
Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p
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- 2023
5. Fibulin-3 is necessary to prevent cardiac rupture following myocardial infarction
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Murtha, Lucy A., Hardy, Sean A., Mabotuwana, Nishani S., Bigland, Mark J., Bailey, Taleah, Raguram, Kalyan, Liu, Saifei, Ngo, Doan T., Sverdlov, Aaron L., Tomin, Tamara, Birner-Gruenberger, Ruth, Hume, Robert D., Iismaa, Siiri E., Humphreys, David T., Patrick, Ralph, Chong, James J. H., Lee, Randall J., Harvey, Richard P., Graham, Robert M., Rainer, Peter P., and Boyle, Andrew J.
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- 2023
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6. Long Term Impact of Epicardial Left Atrial Appendage Ligation on Systemic Hemostasis: LAA HOMEOSTASIS-2
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Bartus, Krzysztof, Kanuri, Sri Harsha, Litwinowicz, Radoslaw, Elbey, Mehmet Ali, Natorska, Joanna, Zabczyk, Michal, Bartus, Magdalena, Kapelak, Boguslaw, Gopinnathannair, Rakesh, Garg, Jalaj, Turagam, Mohit K, Malecki, Maciej T, Lee, Randall J, and Lakkireddy, Dhanunjaya
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Biomedical and Clinical Sciences ,Clinical Sciences ,Cardiovascular ,Heart Disease ,left atrial appendage closure ,LARIAT ,blood pressure ,neurohormonal changes ,systemic hemostasis ,Biomedical and clinical sciences - Abstract
Recent data suggest that epicardial left atrial appendage closure (LAAC) is associated with several short-term neurohormonal effects. However, the long-term effects are currently unknown. To investigate the effects of percutaneous epicardial left atial appendage (LAA) exclusion using LARIAT on neurohormonal profiles at long-term follow-up. In a prospective single centre study, 60 patients with long-standing, persistent atrial fibrillation (AF) LARIAT were treated. The major hormones of the adrenergic system, renin-angiotensin-aldosterone system (RAAS), and natriuretic peptides were assessed before the intervention and at regular intervals during the following two years. In patients with epicardial LAAC, atrial natriuretic peptide (ANP) levels were significantly increased from baseline at 24 h and decreased at 7 days, 1 month, and 3 months, while remaining unchanged at 12 and 24 months. Noradrenaline levels were significantly lower at 24 h, 7 days, 1 month, 6 months, 12 months, and 24 months, while epinephrine levels decreased significantly at 1 month, 6 months, 12 months, and 24 months. Plasma renin activity significantly decreased at 7 days, 1 month, 6 months, 12 months, and 24 months, while aldosterone levels significantly decreased at 6 months, 12 months, and 24 months. Endothelin-1 and vasopressin showed a significant increase and decrease, respectively, at 24 h, 7 days, 1 month, 6 months, 12 months, and 24 months. There was also a significant decrease in systolic and diastolic blood pressure at 3 months, 6 months, 1 year, and 2 years after the intervention. Epicardial LAAC in AF patients is associated with persistent neurohormonal changes favouring blood pressure reduction.
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- 2022
7. Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial
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Ciuffo, Luisa, Tung, Monica, Dukes, Jonathan W., Vittinghoff, Eric, Moss, Joshua D., Lee, Randall J., Lee, Byron K., Tseng, Zian H., Vedantham, Vasanth, Olgin, Jeffrey E., Scheinman, Melvin M., Hsia, Henry, Ramchandani, Vijay A., Gerstenfeld, Edward P., and Marcus, Gregory M.
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- 2024
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8. A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology
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Marcus, Gregory M, Dukes, Jonathan W, Vittinghoff, Eric, Nah, Gregory, Badhwar, Nitish, Moss, Joshua D, Lee, Randall J, Lee, Byron K, Tseng, Zian H, Walters, Tomos E, Vedantham, Vasanth, Gladstone, Rachel, Fan, Shannon, Lee, Emily, Fang, Christina, Ogomori, Kelsey, Hue, Trisha, Olgin, Jeffrey E, Scheinman, Melvin M, Hsia, Henry, Ramchandani, Vijay A, and Gerstenfeld, Edward P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Alcoholism ,Alcohol Use and Health ,Heart Disease ,Cardiovascular ,Substance Misuse ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Blood Alcohol Content ,Cardiac Electrophysiology ,Double-Blind Method ,Heart Atria ,Heart Conduction System ,Humans ,Pulmonary Veins ,atrial fibrillation ,alcohol ,ablation ,electrophysiology ,lifestyle ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
ObjectivesThis study sought to identify acute changes in human atrial electrophysiology during alcohol exposure.BackgroundThe mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia.MethodsIn this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility.ResultsOf 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed.ConclusionsAcute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).
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- 2021
9. Explainability Metrics of Deep Convolutional Networks for Photoplethysmography Quality Assessment.
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Zhang, Oliver, Ding, Cheng, Pereira, Tania, Xiao, Ran, Gadhoumi, Kais, Meisel, Karl, Lee, Randall J, Chen, Yiran, and Hu, Xiao
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Deep neural network ,PPG signal quality ,biomedical informatics ,Measurement ,Deep learning ,Annotations ,Convolution ,Biological system modeling ,Neural networks ,Data models ,Information and Computing Sciences ,Engineering ,Technology - Abstract
Photoplethysmography (PPG) is a noninvasive way to monitor various aspects of the circulatory system, and is becoming more and more widespread in biomedical processing. Recently, deep learning methods for analyzing PPG have also become prevalent, achieving state of the art results on heart rate estimation, atrial fibrillation detection, and motion artifact identification. Consequently, a need for interpretable deep learning has arisen within the field of biomedical signal processing. In this paper, we pioneer novel explanatory metrics which leverage domain-expert knowledge to validate a deep learning model. We visualize model attention over a whole testset using saliency methods and compare it to human expert annotations. Congruence, our first metric, measures the proportion of model attention within expert-annotated regions. Our second metric, Annotation Classification, measures how much of the expert annotations our deep learning model pays attention to. Finally, we apply our metrics to compare between a signal based model and an image based model for PPG signal quality classification. Both models are deep convolutional networks based on the ResNet architectures. We show that our signal-based one dimensional model acts in a more explainable manner than our image based model; on average 50.78% of the one dimensional model's attention are within expert annotations, whereas 36.03% of the two dimensional model's attention are within expert annotations. Similarly, when thresholding the one dimensional model attention, one can more accurately predict if each pixel of the PPG is annotated as artifactual by an expert. Through this testcase, we demonstrate how our metrics can provide a quantitative and dataset-wide analysis of how explainable the model is.
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- 2021
10. A Randomized Trial of High vs Standard Power Radiofrequency Ablation for Pulmonary Vein Isolation: SHORT-AF
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Lee, Adam C., Voskoboinik, Alex, Cheung, Christopher C., Yogi, Sarah, Tseng, Zian H., Moss, Joshua D., Dewland, Thomas A., Lee, Byron K., Lee, Randall J., Hsia, Henry H., Marcus, Gregory M., Vedantham, Vasanth, Chieng, David, Kistler, Peter M., Dillon, William, Vittinghoff, Eric, and Gerstenfeld, Edward P.
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- 2023
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11. Giant Left Atrium Associated with Massive Thrombus Formation 14 Years after Orthotopic Heart Transplantation.
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Bartus, Krzysztof, Litwinowicz, Radoslaw, Kapelak, Boguslaw, Filip, Grzegorz, Wierzbicki, Karol, and Lee, Randall J
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Atrial Fibrilation ,Echocardiography ,Heart Atria ,Heart Transplantation ,Magnetic Resonance Imaging ,Sutures ,Thromboembolism ,Thrombosis ,Cardiovascular System & Hematology - Abstract
We report the case of a 60-year-old patient who underwent orthotopic heart transplant 14 years earlier. Routine echocardiography showed giant masses in the left atrium. There were no symptoms or thromboembolic events in the past. Magnetic resonance imaging study revealed very enlarged left atrium (8.7 × 10.6 cm) occupied by irregular smooth mass (7 × 5 × 6.1 cm) with a stalk that was attached to the posterior left atrial wall in the area of graft suture lines. Intraoperative examination revealed a massive thrombus (12 × 10 cm) that filled almost the entire left atrial area.
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- 2020
12. The Strengths and Weaknesses of Left Atrial Appendage Ligation or Exclusion (LARIAT, AtriaClip, Surgical Suture)
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Lee, Randall J. and Hanke, Thorsten
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- 2023
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13. Randomized Comparison of a Radiofrequency Wire Versus a Radiofrequency Needle System for Transseptal Puncture
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Dewland, Thomas A., Gerstenfeld, Edward P., Moss, Joshua D., Lee, Adam C., Vedantham, Vasanth, Lee, Randall J., Tseng, Zian H., Hsia, Henry H., Lee, Byron K., Wall, Grace C., Chang, Kathleen R., Yang, Michelle H., and Marcus, Gregory M.
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- 2023
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14. Photoplethysmography based atrial fibrillation detection: a review
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Pereira, Tania, Tran, Nate, Gadhoumi, Kais, Pelter, Michele M, Do, Duc H, Lee, Randall J, Colorado, Rene, Meisel, Karl, and Hu, Xiao
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Health Services and Systems ,Health Sciences ,Cardiovascular ,Prevention ,Stroke ,Networking and Information Technology R&D (NITRD) ,Brain Disorders ,Clinical Research ,Heart Disease ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Good Health and Well Being ,Networking and Information Technology R&D ,Diagnosis ,Risk factors ,Health services and systems - Abstract
Atrial fibrillation (AF) is a cardiac rhythm disorder associated with increased morbidity and mortality. It is the leading risk factor for cardioembolic stroke and its early detection is crucial in both primary and secondary stroke prevention. Continuous monitoring of cardiac rhythm is today possible thanks to consumer-grade wearable devices, enabling transformative diagnostic and patient management tools. Such monitoring is possible using low-cost easy-to-implement optical sensors that today equip the majority of wearables. These sensors record blood volume variations-a technology known as photoplethysmography (PPG)-from which the heart rate and other physiological parameters can be extracted to inform about user activity, fitness, sleep, and health. Recently, new wearable devices were introduced as being capable of AF detection, evidenced by large prospective trials in some cases. Such devices would allow for early screening of AF and initiation of therapy to prevent stroke. This review is a summary of a body of work on AF detection using PPG. A thorough account of the signal processing, machine learning, and deep learning approaches used in these studies is presented, followed by a discussion of their limitations and challenges towards clinical applications.
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- 2020
15. Development of Injectable Amniotic Membrane Matrix for Postmyocardial Infarction Tissue Repair.
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Henry, Jeffrey JD, Delrosario, Lawrence, Fang, Jun, Wong, Sze Yue, Fang, Qizhi, Sievers, Richard, Kotha, Surya, Wang, Aijun, Farmer, Diana, Janaswamy, Praneeth, Lee, Randall J, and Li, Song
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Myocardium ,Amnion ,Cells ,Cultured ,Extracellular Matrix ,Epithelial Cells ,Animals ,Cattle ,Humans ,Rats ,Sprague-Dawley ,Myocardial Infarction ,Fibrosis ,Collagen ,Glycosaminoglycans ,Cardiotonic Agents ,Hydrogels ,Tissue Engineering ,Injections ,Materials Testing ,Pregnancy ,Female ,amniotic membranes ,decellularization ,hydrogels ,myocardial infarctions ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Regenerative Medicine ,Bioengineering ,Heart Disease ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Medicinal and Biomolecular Chemistry ,Biomedical Engineering ,Medical Biotechnology - Abstract
Ischemic heart disease represents the leading cause of death worldwide. Heart failure following myocardial infarction (MI) is associated with severe fibrosis formation and cardiac remodeling. Recently, injectable hydrogels have emerged as a promising approach to repair the infarcted heart and improve heart function through minimally invasive administration. Here, a novel injectable human amniotic membrane (hAM) matrix is developed to enhance cardiac regeneration following MI. Human amniotic membrane is isolated from human placenta and engineered to be a thermoresponsive, injectable gel around body temperature. Ultrasound-guided injection of hAM matrix into rat MI hearts significantly improves cardiac contractility, as measured by ejection fraction (EF), and decrease fibrosis. The results of this study demonstrate the feasibility of engineering as an injectable hAM matrix and its efficacy in attenuating degenerative changes in cardiac function following MI, which may have broad applications in tissue regeneration.
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- 2020
16. Generalizability of SuperAlarm via Cross-Institutional Performance Evaluation
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Xiao, Ran, Do, Duc, Ding, Cheng, Meisel, Karl, Lee, Randall J, and Hu, Xiao
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Information and Computing Sciences ,Bioengineering ,Networking and Information Technology R&D (NITRD) ,Patient Safety ,Generic health relevance ,Good Health and Well Being ,Biomedical monitoring ,Training ,Monitoring ,Predictive models ,Medical diagnostic imaging ,Medical services ,Prediction algorithms ,Patient monitoring ,predictive models ,biomedical informatics ,Engineering ,Technology ,Information and computing sciences - Abstract
Bedside patient monitors are ubiquitous tools in modern critical care units to provide timely patient status. However, current systems suffer from high volume of false alarms leading to alarm fatigue, one of top technical hazards in clinical settings. Many studies are racing to develop improved algorithms towards precision patient monitoring, while little has been done to investigate the aspect of algorithm generalizability across different health institutions. Our group has been developing an evolving framework termed SuperAlarm that extracts multivariate patterns in data streams (monitor alarms, electronic health records and physiologic waveforms) of modern health enterprise to predict patient deterioration and has demonstrated great potential in mitigating alarm fatigue. In this study, we further investigate the generalizability of SuperAlarm by designing a comprehensive approach to achieve performance comparison in predicting in-hospital code blue (CB) events across two health institutions. SuperAlarm model trained with alarm data in one institution is tested on both internal and external test sets. Results show comparable performance with sensitivity up to 80% within one-hour window of events and over 90% in reduction of false alarms in both institutions. Cross-institutional performance agreement can be further improved by predicting a more stringent CB subtype (cardiopulmonary arrest), with internal sensitivity lying within 95% confident interval of external one up to 8-hour before event onset. The cross-institutional performance comparison offers first-hand knowledge on both advantages and challenges in generalizing a prediction algorithm across different institutions, which hold key information to guide the design of model training and deployment strategy.
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- 2020
17. The Value of Programmed Ventricular Extrastimuli From the Right Ventricular Basal Septum During Supraventricular Tachycardia
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Higuchi, Satoshi, Ito, Hiroyuki, Gerstenfeld, Edward P., Lee, Adam C., Lee, Byron K., Marcus, Gregory M., Hsia, Henry H., Moss, Joshua D., Lee, Randall J., Dewland, Thomas A., Vedantham, Vasanth, Tseng, Zian H., Patel, Akash R., Tanel, Ronn E., Badhwar, Nitish, Pellegrini, Cara N., Kawamura, Mitsuharu, Shoda, Morio, Hwang, Chun, Refaat, Marwan M., and Scheinman, Melvin M.
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- 2023
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18. Engineering stem cell therapeutics for cardiac repair
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Fang, Jun, Li, Jennifer J., Zhong, Xintong, Zhou, Yue, Lee, Randall J., Cheng, Ke, and Li, Song
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- 2022
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19. Novel role of extracellular matrix protein 1 (ECM1) in cardiac aging and myocardial infarction
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Hardy, Sean A, Mabotuwana, Nishani S, Murtha, Lucy A, Coulter, Brianna, Sanchez-Bezanilla, Sonia, Al-Omary, Mohammed S, Senanayake, Tharindu, Loering, Svenja, Starkey, Malcolm, Lee, Randall J, Rainer, Peter P, Hansbro, Philip M, and Boyle, Andrew J
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Biomedical and Clinical Sciences ,Engineering ,Cardiovascular Medicine and Haematology ,Biomedical Engineering ,Medical Physiology ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Heart Disease ,Aging ,Biotechnology ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Extracellular Matrix Proteins ,Female ,Gene Expression Regulation ,Heart Ventricles ,Humans ,Male ,Mice ,Myocardial Infarction ,Myocardium ,General Science & Technology - Abstract
IntroductionThe prevalence of heart failure increases in the aging population and following myocardial infarction (MI), yet the extracellular matrix (ECM) remodeling underpinning the development of aging- and MI-associated cardiac fibrosis remains poorly understood. A link between inflammation and fibrosis in the heart has long been appreciated, but has mechanistically remained undefined. We investigated the expression of a novel protein, extracellular matrix protein 1 (ECM1) in the aging and infarcted heart.MethodsYoung adult (3-month old) and aging (18-month old) C57BL/6 mice were assessed. Young mice were subjected to left anterior descending artery-ligation to induce MI, or transverse aortic constriction (TAC) surgery to induce pressure-overload cardiomyopathy. Left ventricle (LV) tissue was collected early and late post-MI/TAC. Bone marrow cells (BMCs) were isolated from young healthy mice, and subject to flow cytometry. Human cardiac fibroblast (CFb), myocyte, and coronary artery endothelial & smooth muscle cell lines were cultured; human CFbs were treated with recombinant ECM1. Primary mouse CFbs were cultured and treated with recombinant angiotensin-II or TGF-β1. Immunoblotting, qPCR and mRNA fluorescent in-situ hybridization (mRNA-FISH) were conducted on LV tissue and cells.ResultsECM1 expression was upregulated in the aging LV, and in the infarct zone of the LV early post-MI. No significant differences in ECM1 expression were found late post-MI or at any time-point post-TAC. ECM1 was not expressed in any resident cardiac cells, but ECM1 was highly expressed in BMCs, with high ECM1 expression in granulocytes. Flow cytometry of bone marrow revealed ECM1 expression in large granular leucocytes. mRNA-FISH revealed that ECM1 was indeed expressed by inflammatory cells in the infarct zone at day-3 post-MI. ECM1 stimulation of CFbs induced ERK1/2 and AKT activation and collagen-I expression, suggesting a pro-fibrotic role.ConclusionsECM1 expression is increased in ageing and infarcted hearts but is not expressed by resident cardiac cells. Instead it is expressed by bone marrow-derived granulocytes. ECM1 is sufficient to induce cardiac fibroblast stimulation in vitro. Our findings suggest ECM1 is released from infiltrating inflammatory cells, which leads to cardiac fibroblast stimulation and fibrosis in aging and MI. ECM1 may be a novel intermediary between inflammation and fibrosis.
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- 2019
20. The Strengths and Weaknesses of Left Atrial Appendage Ligation or Exclusion (LARIAT, AtriaClip, Surgical Suture)
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Lee, Randall J. and Hanke, Thorsten
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- 2022
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21. Premature Atrial Contraction Location and Atrial Fibrillation Inducibility
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Howell, Stacey J., Dukes, Jonathan W., Vittinghoff, Eric, Tang, Janet J., Moss, Joshua D., Lee, Randall J., Lee, Byron K., Tseng, Zian H., Vedantham, Vasanth, Olgin, Jeffrey E., Scheinman, Melvin M., Hsia, Henry, Gerstenfeld, Edward P., and Marcus, Gregory M.
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- 2023
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22. Percutaneous epicardial approach for LAA ligation
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Sanchez, José M., Lee, Adam, Bartus, Krzysztof, and Lee, Randall J.
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- 2021
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23. Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction.
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Le, Long V, Mohindra, Priya, Fang, Qizhi, Sievers, Richard E, Mkrtschjan, Michael A, Solis, Christopher, Safranek, Conrad W, Russell, Brenda, Lee, Randall J, and Desai, Tejal A
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Myocardium ,Cell Line ,Animals ,Humans ,Mice ,Rats ,Rats ,Sprague-Dawley ,Myocardial Infarction ,Fibrosis ,Hyaluronic Acid ,Tissue Engineering ,Microspheres ,Cellular Reprogramming Techniques ,Biomaterials ,Cardiovascular disease ,Mechanotransduction ,Photolithography ,Tissue engineering ,Bioengineering ,Regenerative Medicine ,Cardiovascular ,Heart Disease ,Heart Disease - Coronary Heart Disease ,5.2 Cellular and gene therapies ,Development of treatments and therapeutic interventions ,Biomedical Engineering - Abstract
Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.
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- 2018
24. Subxiphoid Hybrid Approach for Epicardial/Endocardial Ablation and LAA Exclusion in Patients with Persistent and Longstanding Atrial Fibrillation.
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Badhwar, Nitish, Al-Dosari, Ghannam, Dukes, Jonathan, and Lee, Randall J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Heart Disease ,Cardiovascular ,Atrial Fibrillation ,Hybrid epicardial/endocardial ablation ,LAA ligation - Abstract
Two patients with long-standing atrial fibrillation (AF) refractory to medical management and with prior pulmonary vein isolation underwent a new hybrid epicardial/endocardial subxyphoid approach for AF ablation and left atrial appendage (LAA) ligation. Pulmonary vein and LA posterior wall isolation, as well as LAA exclusion were achieved in both patients. There were no procedural complications. Both patients remain in sinus rhythm. Both patients are off antiarrhythmic medications.
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- 2018
25. Long term outcomes after left atrial appendage closure with the LARIAT device—Stroke risk reduction over five years follow-up
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Litwinowicz, Radoslaw, Bartus, Magdalena, Burysz, Marian, Brzeziński, Maciej, Suwalski, Piotr, Kapelak, Boguslaw, Vuddanda, Venkat, Lakkireddy, Dhanunjaya, Lee, Randall J, Trabka, Rafal, and Bartus, Krzysztof
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Clinical Research ,Cardiovascular ,Prevention ,Brain Disorders ,Heart Disease ,Stroke ,Hematology ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Good Health and Well Being ,Adult ,Aged ,Aged ,80 and over ,Atrial Appendage ,Female ,Follow-Up Studies ,Heart Diseases ,Humans ,Male ,Middle Aged ,Postoperative Complications ,Prospective Studies ,Time Factors ,Treatment Outcome ,Young Adult ,General Science & Technology - Abstract
INTRODUCTION:Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). MATERIAL AND METHODS:A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. RESULTS:The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. CONCLUSIONS:Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk.
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- 2018
26. Abstract 9803: Randomized Comparison of a Radiofrequency Wire versus a Radiofrequency Needle System for Transseptal Puncture
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Dewland, Thomas A, GERSTENFELD, Edward, Moss, Joshua, Lee, Adam C, Vedantham, Vasanth, Lee, Randall J, Tseng, Zian, Hsia, Henry H, lee, byron K, Wall, Grace, Chang, Kathleen, Yang, Michelle, and Marcus, Gregory M
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- 2022
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27. Aging is protective against pressure overload cardiomyopathy via adaptive extracellular matrix remodeling.
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Geng, Xiaoyong, Hwang, Joy, Ye, Jianqin, Shih, Henry, Coulter, Brianna, Naudin, Crystal, Jun, Kristine, Sievers, Richard, Yeghiazarians, Yerem, Lee, Randall J, and Boyle, Andrew J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Aging ,Cardiovascular ,Heart Disease ,Good Health and Well Being ,heart failure ,pressure overload ,cardiac fibrosis ,Cardiovascular medicine and haematology - Abstract
When challenged by hemodynamic stress, aging hearts respond differently to young hearts. Preclinical models of heart disease should take into account the effects of age. However, in the transverse aortic constriction (TAC) model of pressure-overload cardiomyopathy, the larger aorta of aging mice has not previously been taken into account. First, we studied the aortic size in mice, and found that the aortic cross-sectional area (CSA) is 28% larger in aging mice than in young adult mice (P=0.001). We then performed TAC to make the same proportional reduction in CSA in young and aging mice. This produced the same pressure gradient across the constriction and the same rise in B-type natriuretic peptide expression. Young mice showed acute deterioration in systolic function assessed by pressure-volume loops, progressive LV remodeling on echocardiography, and a 50% mortality at 12 weeks post-TAC. In contrast, aging mice showed no acute deterioration in systolic function, much less ventricular remodeling and were protected from death. Aging mice also showed significantly increased levels of matrix metalloproteinase-3 (MMP-3; 3.2 fold increase, P
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- 2017
28. The QT Interval as a Noninvasive Marker of Atrial Refractoriness
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NGUYEN, KAYLIN T, GLADSTONE, RACHEL A, DUKES, JONATHAN W, NAZER, BABAK, VITTINGHOFF, ERIC, BADHWAR, NITISH, VEDANTHAM, VASANTH, GERSTENFELD, EDWARD P, LEE, BYRON K, LEE, RANDALL J, TSENG, ZIAN H, OLGIN, JEFFREY E, SCHEINMAN, MELVIN M, and MARCUS, GREGORY M
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Heart Disease ,Clinical Research ,Cardiovascular ,Adult ,Aged ,Aged ,80 and over ,Atrial Fibrillation ,Biomarkers ,Diagnosis ,Computer-Assisted ,Electrocardiography ,Female ,Humans ,Long QT Syndrome ,Male ,Middle Aged ,Reproducibility of Results ,Risk Assessment ,Sensitivity and Specificity ,atrial fibrillation ,refractory period ,QT interval ,Biomedical Engineering ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Clinical sciences - Abstract
BackgroundAtrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP).MethodsIn paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length.ResultsIn 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP.ConclusionsThe QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies.
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- 2016
29. Subxiphoid Hybrid Epicardial-Endocardial Atrial Fibrillation Ablation and LAA Ligation: Initial Sub-X Hybrid MAZE Registry Results
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Ellis, Christopher R., Badhwar, Nitish, Tschopp, David, Danter, Matthew, Jackson, Gregory G., Kerendi, Faraz, Walters, Tomas, Fang, Qizhi, Deuse, Tobias, Beygui, Ramin, and Lee, Randall J.
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- 2020
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30. Pulmonary Vein Isolation With or Without Left Atrial Appendage Ligation in Atrial Fibrillation: The aMAZE Randomized Clinical Trial.
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Lakkireddy, Dhanunjaya R., Wilber, David J., Mittal, Suneet, Tschopp, David, Ellis, Christopher R., Rasekh, Abdi, Hounshell, Troy, Evonich, Rudy, Chandhok, Sheetal, Berger, Ronald D., Horton, Rodney, Hoskins, Michael H., Calkins, Hugh, Yakubov, Steven J., Simons, Pamela, Saville, Benjamin R., and Lee, Randall J.
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PULMONARY veins ,LEFT heart atrium ,ATRIAL fibrillation ,LEFT atrial appendage closure ,CLINICAL trials ,P-waves (Electrocardiography) - Abstract
Key Points: Question: Does left atrial appendage ligation improve catheter ablation treatment of nonparoxysmal atrial fibrillation? Findings: In this randomized clinical trial of 610 adults, primary effectiveness was based on freedom from atrial arrhythmias at 12 months and was not statistically different between those receiving percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation and pulmonary vein isolation alone (64.3% vs 59.9%; difference, 4.3% [bayesian 95% credible interval, −4.2% to 13.2%]). Primary safety was met, with a 30-day serious adverse event rate of 3.4%. At 12 months after pulmonary vein isolation, there was complete closure in 84% of patients who underwent left atrial appendage, and 99% had less than or equal to 5 mm of residual communication with the left atrium. Meaning: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation met prespecified safety criteria, but did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone. Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and Participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and Measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, −4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and Relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT02513797 This multicenter randomized clinical trial examines the effectiveness and safety of left atrial appendage ligation plus pulmonary vein isolation for nonparoxysmal atrial fibrillation treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Anatomic Considerations for Epicardial and Endocardial Left Atrial Appendage Closure
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Voskoboinik, Aleksandr and Lee, Randall J.
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- 2020
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32. Left atrial appendage ligation in patients with atrial fibrillation leads to a decrease in atrial dispersion.
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Kawamura, Mitsuharu, Scheinman, Melvin M, Lee, Randall J, and Badhwar, Nitish
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Atrial Appendage ,Heart Conduction System ,Humans ,Atrial Fibrillation ,Echocardiography ,Ultrasonography ,Interventional ,Treatment Outcome ,Cardiac Surgical Procedures ,Ligation ,Follow-Up Studies ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Atrial Remodeling ,P wave ,atrial fibrillation ,atrial remodeling ,left atrial appendage ,ligation ,Heart Disease ,Cardiovascular ,Clinical Research ,2.1 Biological and endogenous factors ,Cardiorespiratory Medicine and Haematology - Abstract
BackgroundLeft atrial appendage (LAA) exclusion has been performed in patients with atrial fibrillation (AF) to prevent thrombus formation and subsequent cardioembolic events. Left atrial electrical remodeling is a recognized factor in the recurrence of AF. The effects of LAA exclusion on P-wave characteristics and left atrial electrical remodeling have not been well described. The purpose of this study was to evaluate the effect of LAA ligation on P-wave morphology in patients with AF.Methods and resultsFifteen patients who were in sinus rhythm during the LAA ligation procedure were included in the study. We evaluated the P-wave characteristics, including P-wave duration, P-wave amplitude, PQ interval, and P-wave dispersion, before and after ligation. Eleven patients had paroxysmal AF and 4 patients had persistent AF (12 male patients and 3 female patients). P-wave duration immediately after ligation was significantly shorter compared with baseline in all limb leads except lead aVR (P
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- 2015
33. Discrete microstructural cues for the attenuation of fibrosis following myocardial infarction.
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Pinney, James R, Du, Kim T, Ayala, Perla, Fang, Qizhi, Sievers, Richard E, Chew, Patrick, Delrosario, Lawrence, Lee, Randall J, and Desai, Tejal A
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Myocardium ,3T3 Cells ,Fibroblasts ,Animals ,Mice ,Rats ,Sprague-Dawley ,Myocardial Infarction ,Fibrosis ,Polyethylene Glycols ,Methacrylates ,Collagen ,Biocompatible Materials ,Tissue Engineering ,Female ,Microtechnology ,Cardiac tissue engineering ,ECM ,Photolithography ,Polyethylene glycol dimethacrylate ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Heart Disease ,Biotechnology ,Biomedical Engineering - Abstract
Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. We have developed a therapeutic materials strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructures to mechanically alter the microenvironment. Polymeric microstructures were fabricated using photolithographic techniques and studied in a three-dimensional culture model of the fibrotic environment and by direct injection into the infarct zone of adult rats. Here, we show dose-dependent down-regulation of expression of genes associated with the mechanical fibrotic response in the presence of microstructures. Injection of this microstructured material into the infarct zone decreased levels of collagen and TGF-β, increased elastin deposition and vascularization in the infarcted region, and improved functional outcomes after six weeks. Our results demonstrate the efficacy of these discrete anti-fibrotic microstructures and suggest a potential therapeutic materials approach for combatting pathologic fibrosis.
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- 2014
34. An overview of current and emerging devices for percutaneous left atrial appendage closure
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Chow, Danny H.F., Wong, Yam-Hong, Park, Jai-Wun, Lam, Yat-Yin, De Potter, Tom, Rodés-Cabau, Josep, Asmarats, Lluis, Sandri, Marcus, Sideris, Eleftherios, McCaw, Trevor, Lee, Randall J., Sievert, Horst, Søndergaard, Lars, and De Backer, Ole
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- 2019
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35. The effects of LAA ligation on LAA electrical activity
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Han, Frederick T, Bartus, Krzysztof, Lakkireddy, Dhanunjaya, Rojas, Francia, Bednarek, Jacek, Kapelak, Boguslaw, Bartus, Magdalena, Sadowski, Jerzy, Badhwar, Nitish, Earnest, Mathew, Valderrabano, Miguel, and Lee, Randall J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Cardiovascular ,Heart Disease ,Aged ,Atrial Fibrillation ,Cardiac Surgical Procedures ,Electrocardiography ,Follow-Up Studies ,Heart Atria ,Heart Conduction System ,Humans ,Ligation ,Male ,Retrospective Studies ,Time Factors ,Treatment Outcome ,Atrial fibrillation ,Left atrial appendage ,Left atrial appendage ligation ,Biomedical Engineering ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundThe arrhythmic role of the left atrial appendage (LAA) has been implicated in the maintenance of persistent atrial fibrillation. LAA isolation with catheter ablation has been successful but is limited by the risk of tamponade and electromechanical dissociation with the potential for LAA thrombus formation.ObjectiveTo assess whether LAA ligation results in LAA electrical isolation.MethodsA total of 68 patients with contraindication or intolerance to oral anticoagulation therapy underwent LAA ligation with the LARIAT suture delivery device. Patients had unipolar [n = 30(44%)] or bipolar [n = 38(56%)] voltage measurements pre- and post-LAA ligation.ResultsAll 68 patients underwent successful LAA ligation. There was a statistically significant reduction in the mean LAA voltage from pre-ligation (unipolar pre-ligation voltage 1.1 ± 0.53 mV; bipolar pre-ligation voltage 4.7 ± 2.83 mV) to post-ligation (unipolar post-ligation voltage 0.3 ± 0.38 mV; bipolar post-ligation voltage 0.6 ± 0.27 mV). Ninety-four percent of the patients had a reduction in the LAA voltage after the closure of the snare, with 10 of 30 (33%) of the patients having complete elimination of LAA voltage with the initial tightening of the suture. Pacing from the LAA after the closure of the snare resulted in lack of capture of the left atrium in 28 of 31 patients.ConclusionsThe snare closure of the LAA using the LARIAT device produces an acute reduction in the LAA voltage and inhibits the capture of the left atrium during LAA pacing. Future studies are needed to determine whether LAA ligation affects atrial fibrillation burden.
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- 2014
36. Hybrid Endo-Epicardial Therapies for Advanced Atrial Fibrillation.
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Wong, Christopher X., Buch, Eric F., Beygui, Ramin, and Lee, Randall J.
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ATRIAL fibrillation ,ATRIAL flutter ,HEALTH care teams ,ABLATION techniques ,CATHETER ablation ,NOSOLOGY - Abstract
Atrial fibrillation (AF) is a growing health problem that increases morbidity and mortality, and in most patients progresses to more advanced diseases over time. Recent research has examined the underlying mechanisms, risk factors, and progression of AF, leading to updated AF disease classification schemes. Although endocardial catheter ablation is effective for early-stage paroxysmal AF, it consistently achieves suboptimal outcomes in patients with advanced AF. Identification of the factors that lead to the increased risk of treatment failure in advanced AF has spurred the development and adoption of hybrid ablation therapies and collaborative heart care teams that result in higher long-term arrhythmia-free survival. Patients with non-paroxysmal AF, atrial remodeling, comorbidities, or AF otherwise deemed difficult to treat may find hybrid treatment to be the most effective option. Future research of hybrid therapies in advanced AF patient populations, including those with dual diagnoses, may provide further evidence establishing the safety and efficacy of hybrid endo-epicardial ablation as a first line treatment. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Postoperative Coagulation Changes in Patients after Epicardial Left Atrial Appendage Occlusion Varies Based on the Left Atrial Appendage Size.
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Batko, Jakub, Rusinek, Jakub, Słomka, Artur, Litwinowicz, Radosław, Burysz, Marian, Bartuś, Magdalena, Lakkireddy, Dhanunjaya R., Lee, Randall J., Natorska, Joanna, Ząbczyk, Michał, Kapelak, Bogusław, and Bartuś, Krzysztof
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LEFT heart atrium ,BLOOD coagulation ,BLOOD coagulation factors ,OCCLUSION (Chemistry) ,BODY size ,COMPUTED tomography ,PLASMINOGEN ,BLOOD testing - Abstract
Left atrial appendage occlusion affects systemic coagulation parameters, leading to additional patient-related benefits. The aim of this study was to investigate the differences in coagulation factor changes 6 months after epicardial left atrial appendage occlusion in patients with different LAA morphometries. This is the first study to analyze these relationships in detail. A prospective study of 22 consecutive patients was performed. Plasminogen, fibrinogen, tPA concentration, PAI-1, TAFI and computed tomography angiograms were performed. Patients were divided into subgroups based on left atrial appendage body and orifice diameter enlargement. The results of blood tests at baseline and six-month follow-up were compared. In a population with normal LAA body size and normal orifice diameter size, a significant decrease in analyzed clotting factors was observed between baseline and follow-up for all parameters except plasminogen. A significant decrease between baseline and follow-up was observed with enlarged LAA body size in all parameters except TAFI, in which it was insignificant and plasminogen, in which a significant increase was observed. Occlusion of the left atrial appendage is beneficial for systemic coagulation. Patients with a small LAA may benefit more from LAA closure in terms of stabilizing their coagulation factors associated with potential thromboembolic events in the future. [ABSTRACT FROM AUTHOR]
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- 2024
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38. The Effects of Aging on Apoptosis Following Myocardial Infarction
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Boyle, Andrew J, Hwang, Joy, Ye, Jianqin, Shih, Henry, Jun, Kristine, Zhang, Yan, Fang, Qizhi, Sievers, Richard, Yeghiazarians, Yerem, and Lee, Randall J
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Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Aging ,Underpinning research ,1.1 Normal biological development and functioning ,Good Health and Well Being ,Animals ,Apoptosis ,Caspase 3 ,Male ,Mice ,Mice ,Inbred C57BL ,Myocardial Infarction ,Myocytes ,Cardiac ,Cardiomyocyte ,Heart failure ,Ventricular remodeling ,Cardiorespiratory Medicine and Haematology ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology ,Pharmacology and pharmaceutical sciences - Abstract
BackgroundAging is associated with higher incidence of heart failure and death following myocardial infarction (MI). The molecular and cellular changes that lead to these worse outcomes are not known.Methods and resultsYoung and aging mice underwent induction of MI by LAD ligation. There was a significant increase in mortality in the aging mice. Neither the young nor aging hearts after MI had inducible ventricular tachycardia. Cardiomyocyte apoptosis increases early after MI in young and aging mice, but to a much greater degree in the aging mice. Caspase inhibition with Ac-DEVD-CHO resulted in a 61% reduction in activated caspase-3 and an 84% reduction in apoptosis in cardiomyocytes in young mice (P
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- 2013
39. Algisyl-LVR™ with coronary artery bypass grafting reduces left ventricular wall stress and improves function in the failing human heart
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Lee, Lik Chuan, Wall, Samuel T, Klepach, Doron, Ge, Liang, Zhang, Zhihong, Lee, Randall J, Hinson, Andy, Gorman, Joseph H, Gorman, Robert C, and Guccione, Julius M
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Research ,Aging ,Heart Disease ,Heart Disease - Coronary Heart Disease ,Cardiovascular ,Biomedical Imaging ,Atherosclerosis ,Adult ,Aged ,Alginates ,Biocompatible Materials ,Coronary Artery Bypass ,Dental Impression Materials ,Female ,Follow-Up Studies ,Glucuronic Acid ,Heart Failure ,Heart Ventricles ,Hexuronic Acids ,Humans ,Image Processing ,Computer-Assisted ,Magnetic Resonance Imaging ,Cine ,Male ,Middle Aged ,Models ,Theoretical ,Myocardial Contraction ,Prosthesis Implantation ,Stroke Volume ,Treatment Outcome ,Ventricular Function ,Left ,Congestive heart failure ,Dilated cardiomyopathy ,Coronary artery bypass grafting ,Left ventricular wall stress ,Mathematical modeling ,Magnetic resonance imaging ,Cardiorespiratory Medicine and Haematology ,Public Health and Health Services ,Cardiovascular System & Hematology ,Cardiovascular medicine and haematology - Abstract
BackgroundLeft ventricular (LV) wall stress reduction is a cornerstone in treating heart failure. Large animal models and computer simulations indicate that adding non-contractile material to the damaged LV wall can potentially reduce myofiber stress. We sought to quantify the effects of a novel implantable hydrogel (Algisyl-LVR™) treatment in combination with coronary artery bypass grafting (i.e. Algisyl-LVR™+CABG) on both LV function and wall stress in heart failure patients.Methods and resultsMagnetic resonance images obtained before treatment (n=3), and at 3 months (n=3) and 6 months (n=2) afterwards were used to reconstruct the LV geometry. Cardiac function was quantified using end-diastolic volume (EDV), end-systolic volume (ESV), regional wall thickness, sphericity index and regional myofiber stress computed using validated mathematical modeling. The LV became more ellipsoidal after treatment, and both EDV and ESV decreased substantially 3 months after treatment in all patients; EDV decreased from 264 ± 91 ml to 146 ± 86 ml and ESV decreased from 184 ± 85 ml to 86 ± 76 ml. Ejection fraction increased from 32 ± 8% to 47 ± 18% during that period. Volumetric-averaged wall thickness increased in all patients, from 1.06 ± 0.21 cm (baseline) to 1.3 ± 0.26 cm (3 months). These changes were accompanied by about a 35% decrease in myofiber stress at end-of-diastole and at end-of-systole. Post-treatment myofiber stress became more uniform in the LV.ConclusionsThese results support the novel concept that Algisyl-LVR™+CABG treatment leads to decreased myofiber stress, restored LV geometry and improved function.
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- 2013
40. Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction
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Le, Long V., Mohindra, Priya, Fang, Qizhi, Sievers, Richard E., Mkrtschjan, Michael A., Solis, Christopher, Safranek, Conrad W., Russell, Brenda, Lee, Randall J., and Desai, Tejal A.
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- 2018
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41. Use of Programmed Ventricular Extrastimulus During Supraventricular Tachycardia to Differentiate Atrioventricular Nodal Re-Entrant Tachycardia From Atrioventricular Re-Entrant Tachycardia
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Ito, Hiroyuki, Badhwar, Nitish, Patel, Akash R., Hoffmayer, Kurt S., Moss, Joshua D., Pellegrini, Cara N., Vedantham, Vasanth, Tseng, Zian H., Tanel, Ronn E., Hsia, Henry H., Lee, Randall J., Marcus, Gregory M., Gerstenfeld, Edward P., and Scheinman, Melvin M.
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- 2018
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42. Randomized Trial of Conventional Transseptal Needle Versus Radiofrequency Energy Needle Puncture for Left Atrial Access (the TRAVERSE‐LA Study)
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Hsu, Jonathan C, Badhwar, Nitish, Gerstenfeld, Edward P, Lee, Randall J, Mandyam, Mala C, Dewland, Thomas A, Imburgia, Kourtney E, Hoffmayer, Kurt S, Vedantham, Vasanth, Lee, Byron K, Tseng, Zian H, Scheinman, Melvin M, Olgin, Jeffrey E, and Marcus, Gregory M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Comparative Effectiveness Research ,6.3 Medical devices ,Evaluation of treatments and therapeutic interventions ,Catheter Ablation ,Equipment Design ,Female ,Heart Atria ,Humans ,Male ,Middle Aged ,Needles ,Prospective Studies ,Punctures ,Radio Waves ,Single-Blind Method ,Brockenbrough needle ,comparative effectiveness ,left atrial access ,radiofrequency energy needle ,randomized controlled trial ,transseptal puncture ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology - Abstract
BackgroundTransseptal puncture is a critical step in achieving left atrial (LA) access for a variety of cardiac procedures. Although the mechanical Brockenbrough needle has historically been used for this procedure, a needle employing radiofrequency (RF) energy has more recently been approved for clinical use. We sought to investigate the comparative effectiveness of an RF versus conventional needle for transseptal LA access.Methods and resultsIn this prospective, single-blinded, controlled trial, 72 patients were randomized in a 1:1 fashion to an RF versus conventional (BRK-1) transseptal needle. In an intention-to-treat analysis, the primary outcome was time required for transseptal LA access. Secondary outcomes included failure of the assigned needle, visible plastic dilator shavings from needle introduction, and any procedural complication. The median transseptal puncture time was 68% shorter using the RF needle compared with the conventional needle (2.3 minutes [interquartile range {IQR}, 1.7 to 3.8 minutes] versus 7.3 minutes [IQR, 2.7 to 14.1 minutes], P = 0.005). Failure to achieve transseptal LA access with the assigned needle was less common using the RF versus conventional needle (0/36 [0%] versus 10/36 [27.8%], P < 0.001). Plastic shavings were grossly visible after needle advancement through the dilator and sheath in 0 (0%) RF needle cases and 12 (33.3%) conventional needle cases (P < 0.001). There were no differences in procedural complications (1/36 [2.8%] versus 1/36 [2.8%]).ConclusionsUse of an RF needle resulted in shorter time to transseptal LA access, less failure in achieving transseptal LA access, and fewer visible plastic shavings.
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- 2013
43. Augmentation of Left Ventricular Wall Thickness With Alginate Hydrogel Implants Improves Left Ventricular Function and Prevents Progressive Remodeling in Dogs With Chronic Heart Failure
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Sabbah, Hani N, Wang, Mengjun, Gupta, Ramesh C, Rastogi, Sharad, Ilsar, Itamar, Sabbah, Michael S, Kohli, Smita, Helgerson, Sam, and Lee, Randall J
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Cardiovascular ,Heart Disease ,Aging ,Alginates ,Animals ,Chronic Disease ,Dogs ,Heart Failure ,Heart Ventricles ,Hydrogel ,Polyethylene Glycol Dimethacrylate ,Organ Size ,Prostheses and Implants ,Ventricular Function ,Left ,Ventricular Remodeling ,animal models ,congestive heart failure ,functional mitral regurgitation ,left ventricular function ,pressure-volume relationship ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology - Abstract
ObjectivesThe study tested the hypothesis that augmentation of the left ventricular (LV) wall thickness with direct intramyocardial injections of alginate hydrogel implants (AHI) reduces LV cavity size, restores LV shape, and improves LV function in dogs with heart failure (HF).BackgroundProgressive LV dysfunction, enlargement, and chamber sphericity are features of HF associated with increased mortality and morbidity.MethodsStudies were performed in 14 dogs with HF produced by intracoronary microembolizations (LV ejection fraction [EF]
- Published
- 2013
44. Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.
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Fang, Qizhi, Mok, Pamela Y, Thomas, Anila E, Haddad, Daniel J, Saini, Shereen A, Clifford, Brian T, Kapasi, Neel K, Danforth, Olivia M, Usui, Minako, Ye, Weisheng, Luu, Emmy, Sharma, Rikki, Bartel, Maya J, Pathmanabhan, Jeremy A, Ang, Andrew AS, Sievers, Richard E, Lee, Randall J, and Springer, Matthew L
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Pleiotrophin ,Myoblasts ,Angiogenesis ,Endothelial cells ,Hindlimb ischemia - Abstract
Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.
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- 2013
45. Patients With Atrial Fibrillation Who Are Not on Anticoagulant Treatment Due to Increased Bleeding Risk Are Common and Have a High Risk of Stroke
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Redfors, Björn, Gray, William A., Lee, Randall J., Ellenbogen, Kenneth A., Bonafede, Machaon, and Ben-Yehuda, Ori
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- 2017
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46. An engineered cardiac reporter cell line identifies human embryonic stem cell-derived myocardial precursors.
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Ritner, Carissa, Wong, Sharon SY, King, Frank W, Mihardja, Shirley S, Liszewski, Walter, Erle, David J, Lee, Randall J, and Bernstein, Harold S
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Cell Line ,Myoblasts ,Cardiac ,Humans ,Ventricular Myosins ,Transforming Growth Factor beta ,Myosin Heavy Chains ,Green Fluorescent Proteins ,Gene Expression Profiling ,Protein Engineering ,Signal Transduction ,Wnt Proteins ,Embryonic Stem Cells ,Myoblasts ,Cardiac ,General Science & Technology - Abstract
Unlike some organs, the heart is unable to repair itself after injury. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body. As such, they provide an unprecedented opportunity to treat human diseases characterized by tissue loss. We have identified early myocardial precursors derived from hESCs (hMPs) using an α-myosin heavy chain (αMHC)-GFP reporter line. We have demonstrated by immunocytochemistry and quantitative real-time PCR (qPCR) that reporter activation is restricted to hESC-derived cardiomyocytes (CMs) differentiated in vitro, and that hMPs give rise exclusively to muscle in an in vivo teratoma formation assay. We also demonstrate that the reporter does not interfere with hESC genomic stability. Importantly, we show that hMPs give rise to atrial, ventricular and specialized conduction CM subtypes by qPCR and microelectrode array analysis. Expression profiling of hMPs over the course of differentiation implicate Wnt and transforming growth factor-β signaling pathways in CM development. The identification of hMPs using this αMHC-GFP reporter line will provide important insight into the pathways regulating human myocardial development, and may provide a novel therapeutic reagent for the treatment of cardiac disease.
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- 2011
47. Targeted in vivo extracellular matrix formation promotes neovascularization in a rodent model of myocardial infarction.
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Mihardja, Shirley S, Gao, Dongwei, Sievers, Richard E, Fang, Qizhi, Feng, Jinjin, Wang, Jianming, Vanbrocklin, Henry F, Larrick, James W, Huang, Manley, Dae, Michael, and Lee, Randall J
- Subjects
Extracellular Matrix ,Animals ,Rats ,Rats ,Sprague-Dawley ,Myocardial Reperfusion Injury ,Myocardial Infarction ,Peptide Fragments ,Myosin Heavy Chains ,Fibronectins ,Collagen Type IV ,Antibodies ,Immunoconjugates ,Drug Delivery Systems ,Neovascularization ,Physiologic ,Sprague-Dawley ,Neovascularization ,Physiologic ,General Science & Technology - Abstract
BackgroundThe extracellular matrix plays an important role in tissue regeneration. We investigated whether extracellular matrix protein fragments could be targeted with antibodies to ischemically injured myocardium to promote angiogenesis and myocardial repair.Methodology/principal findingsFour peptides, 2 derived from fibronectin and 2 derived from Type IV Collagen, were assessed for in vitro and in vivo tendencies for angiogenesis. Three of the four peptides--Hep I, Hep III, RGD--were identified and shown to increase endothelial cell attachment, proliferation, migration and cell activation in vitro. By chemically conjugating these peptides to an anti-myosin heavy chain antibody, the peptides could be administered intravenously and specifically targeted to the site of the myocardial infarction. When administered into Sprague-Dawley rats that underwent ischemia-reperfusion myocardial infarction, these peptides produced statistically significantly higher levels of angiogenesis and arteriogenesis 6 weeks post treatment.Conclusions/significanceWe demonstrated that antibody-targeted ECM-derived peptides alone can be used to sufficiently alter the extracellular matrix microenvironment to induce a dramatic angiogenic response in the myocardial infarct area. Our results indicate a potentially new non-invasive strategy for repairing damaged tissue, as well as a novel tool for investigating in vivo cell biology.
- Published
- 2010
48. Comparison of Gene-Transfer Efficiency in Human Embryonic Stem Cells
- Author
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Cao, Feng, Xie, Xiaoyan, Gollan, Timothy, Zhao, Li, Narsinh, Kazim, Lee, Randall J., and Wu, Joseph C.
- Subjects
Medicine & Public Health ,Imaging / Radiology ,Human embryonic stem cell ,Molecular imaging ,Gene transfer ,Plasmid transfection ,Lentivirus transduction - Abstract
Technologies designed to allow manipulation and modification of human embryonic stem (hES) cells are numerous and vary in the complexity of their methods, efficiency, reliability, and safety. The most commonly studied and practiced of these methods include electroporation, lipofection, nucleofection, and lentiviral transduction. However, at present, it is unclear which protocol offers the most efficient and reliable method of gene transfer to hES cells. In this study, a bi-fusion construct with ubiquitin promoter driving enhanced green fluorescent protein reporter and the firefly luciferase (pUb-eGFP-Fluc) along with neomycin selection marker was used for in vitro and in vivo studies. In vitro studies examined the transfection efficiency and viability of each technique using two hES cell lines (male H1 and female H9 cells). Lentiviral transduction demonstrated the highest efficiency (H1: 25.3 ± 4.8%; H9: 22.4 ± 6.5%) with >95% cell viability. Nucleofection demonstrated transfection efficiency of 16.1 ± 3.6% (H1) and 5.8 ± 3.2% (H9). However, minimal transfection efficiency was observed with electroporation (2.1 ± 0.4% (H1) and 1.9 ± 0.3% (H9)) and lipofection (1.5 ± 0.5% (H1) and 1.3 ± 0.2% (H9); P
- Published
- 2010
49. Abstract 12935: Predictors of Long-term Success After Catheter Ablation of Premature Ventricular Complexes
- Author
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Im, Sung Il, Voskoboinik, Aleksandr, Lee, Adam C, higuchi, satoshi, lee, byron, Hsia, Henry H, Moss, Joshua, Vedantham, Vasanth, Marcus, Gregory M, Tseng, zian, Lee, Randall J, scheinman, melvin, and GERSTENFELD, Edward
- Published
- 2020
- Full Text
- View/download PDF
50. Left atrial appendage ligation with the next generation LARIAT+ suture delivery device: Early clinical experience
- Author
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Bartus, Krzysztof, Gafoor, Sameer, Tschopp, David, Foran, John P., Tilz, Roland, Wong, Tom, Lakkireddy, Dhanunjaya, Sievert, Horst, and Lee, Randall J.
- Published
- 2016
- Full Text
- View/download PDF
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